Testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes has been performed in over 70,000 individuals. Like other sequence-based tests, the results can reveal a normal sequence, a clearly deleterious mutation or a sequence variant of uncertain significance (VUS), in which it is not known whether the VUS confers an increased cancer risk. VUS results are confusing and occur in approximately 12% of tests. Their adequate interpretation requires a basic understanding of genetic principles, the laboratory methods utilized and pedigree analysis. No studies, however, have been published that assess the interpretation and clinical recommendations of non-geneticist physicians receiving a VUS result for BRCA gene sequencing and our own clinical experience suggests that many physicians categorize all VUS results as deleterious mutations potentially leading to inappropriate management recommendations. [unreadable] [unreadable] Hypothesis: Non-geneticist physicians do not discriminate between a VUS and a deleterious mutation when making recommendations with regard to breast and ovarian cancer risk management. Study Design: We will optimize and administer to members of the Texas Medical Association (internists, family practitioners, obstetrician-gynecologists, general surgeons, and oncologists) an on-line questionnaire that presents case scenarios that include BRCA test results that are deleterious, negative or have one or more VUS. A control group of experts in cancer genetics will be included. Physicians will be queried on testing options for at-risk individuals in the family, impact of the test result on cancer risk and asked to choose among a range of management options. Statistical analysis will determine whether the "path" of responses to a VUS result is more similar to a clearly deleterious or negative result. These results will be used to develop appropriate CME-eligible educational materials and to design genetic testing report formats that decrease areas of confusion identified in the survey. Relevance: Consistent with the goals of the NHGRI to bring "Genomics to Health" it is imperative that we optimize the appropriate interpretation of sequence-based genetic tests by a variety of physician specialties for use in clinical decision making. With the increasing availability of complex testing modalities, e.g. DNA and RNA gene chips, for a variety of both rare and common diseases, appropriate reporting and physician education must accompany the development of these tests. [unreadable] [unreadable] [unreadable]